Leishmania amazonensis downregulates macrophage iNOS expression via Histone Deacetylase 1 (HDAC1): a novel parasite evasion mechanism.

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Ressource 1Download: Calegari-Silva_et_al-2017-European_Journal_of_Immunology.pdf (2221.06 [Ko])
State: Public
Version: Author's accepted manuscript
Serval ID
serval:BIB_2BD77F8A82A7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Leishmania amazonensis downregulates macrophage iNOS expression via Histone Deacetylase 1 (HDAC1): a novel parasite evasion mechanism.
Journal
European journal of immunology
Author(s)
Calegari-Silva T.C., Vivarini Á.C., Pereira RMS, Dias-Teixeira K.L., Rath C.T., Pacheco ASS, Silva GBL, Pinto CAS, Dos Santos J.V., Saliba A.M., Corbett CEP, de Castro Gomes C.M., Fasel N., Lopes U.G.
ISSN
1521-4141 (Electronic)
ISSN-L
0014-2980
Publication state
Published
Issued date
07/2018
Peer-reviewed
Oui
Volume
48
Number
7
Pages
1188-1198
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The induced expression of nitric oxide synthase (iNOS) controls the intracellular growth of Leishmania in infected macrophages. Histones deacetylases (HDACs) negatively regulate gene expression through the formation of complexes containing transcription factors such as NF-κB p50/50. Herein, we demonstrated the occupancy of p50/p50_HDAC1 to iNOS promoter associated with reduced levels of H3K9Ac. Remarkably, we found increased levels of HDAC1 in L. amazonensis-infected macrophages. HDAC1 upregulation was not found in L. major-infected macrophages. The parasite intracellular load was reduced in HDAC1 knocked-down macrophages, which presented increased nitric oxide levels. HDAC1 silencing led to the occupancy of CBP/p300 to iNOS promoter and the rise of H3K9Ac modification. Importantly, the immunostaining of skin samples from hiporeactive cutaneous leishmaniasis patients infected with L. amazonensis, revealed high levels of HDAC1. In brief, L. amazonensis induces HDAC1 in infected macrophages, which contribute to parasite survival and is associated to hiporeactive stage found in L. amazonensis infected patients.
Keywords
Adolescent, Adult, Cells, Cultured, Child, Extinction, Biological, Female, Histone Deacetylase 1/genetics, Histone Deacetylase 1/metabolism, Host-Parasite Interactions, Humans, Immune Evasion, Leishmania braziliensis/physiology, Leishmaniasis, Cutaneous/genetics, Leishmaniasis, Cutaneous/immunology, Macrophages/immunology, Male, Middle Aged, Nitric Oxide/metabolism, Nitric Oxide Synthase Type II/genetics, Nitric Oxide Synthase Type II/metabolism, Parasite Load, Promoter Regions, Genetic/genetics, Protein Binding, RNA, Small Interfering/genetics, Skin/pathology, Sp1 Transcription Factor/metabolism, Young Adult, HDAC1, Leishmaniasis, Macrophage, Parasitse
Pubmed
Web of science
Create date
19/04/2018 21:03
Last modification date
20/08/2019 14:11
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